Journal Article FZJ-2025-00938

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Autoradiography of Intracerebral Tumours in the Chick Embryo Model: A Feasibility Study Using Different PET Tracers

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2025
Springer Nature Switzerland Cham

Molecular imaging & biology 27(1), 151–162 () [10.1007/s11307-025-01983-9]

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Abstract: Purpose In addition to rodent models, the chick embryo model has gained attention for radiotracer evaluation. Previous studieshave investigated tumours on the chorioallantoic membrane (CAM), but its value for radiotracer imaging of intracerebraltumours has yet to be demonstrated.Procedures Human U87 glioblastoma cells and U87-IDH1 mutant glioma cells were implanted into the brains of chickembryos at developmental day 5. After 12–14 days of tumour growth, blood–brain-barrier integrity was evaluated in vivousing MRI contrast enhancement or ex vivo with Evans blue dye. The tracers O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET)(n = 5), 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine ([18F]FDOPA) (n = 3), or [68Ga] labelled quinoline-based small moleculefibroblast activation protein inhibitor ([68Ga]FAPI-46) (n = 4) were injected intravenously if solid tumours were detectedwith MRI. For time-activity curves for [18F]FET, additional micro PET (μPET) was performed. The chick embryos weresacrificed 60 min post-injection, and cryosections of the tumour-bearing brains were produced and evaluated with autoradiographyand immunohistochemistry.Results Intracerebral tumours were produced with a 100% success rate in viable chick embryos at the experimental endpoint.However, 52% of chick embryos (n = 85) did not survive the procedure to embryonic development day 20. For the evaluatedradiotracers, the tumour-to-brain ratios (TBR) derived from ex vivo autoradiography, as well as the tracer kinetics derivedfrom μPET for intracerebral chick embryo tumours, were comparable to those previously reported in rodents and patients:the TBRmean for [18F]FET was 1.69 ± 0.54 (n = 5), and 3.8 for one hypermetabolic tumour and < 2.0 for two isometabolictumors using [18F]FDOPA, with a TBRmean of 1.92 ± 1,11 (n = 3). The TBRmean of [68Ga]FAPI-46 for intracerebral chickembryo tumours was 19.13 ± 0.64 (n = 4). An intact blood-tumour barrier was observed in one U87-MG tumour (n = 5).Conclusions Radiotracer imaging of intracerebral tumours in the chick embryo offers a fast model for the evaluation of radiotraceruptake, accumulation, and kinetics. Our results indicate a high comparability between intracerebral tumour imagingin chick embryos and xenograft rodent models or brain tumour patients.

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Contributing Institute(s):
  1. Physik der Medizinischen Bildgebung (INM-4)
  2. Jara-Institut Quantum Information (INM-11)
  3. Jülich-Aachen Research Alliance - Translational Brain Medicine (JARA-BRAIN)
  4. Nuklearchemie (INM-5)
Research Program(s):
  1. 5253 - Neuroimaging (POF4-525) (POF4-525)
  2. DFG project G:(GEPRIS)491111487 - Open-Access-Publikationskosten / 2025 - 2027 / Forschungszentrum Jülich (OAPKFZJ) (491111487) (491111487)
  3. DFG project G:(GEPRIS)513201378 - Entwicklung 18F-markierter Positronen-Emissions-Tomographie Tracer für die nicht-invasive Erfassung von Mutationen der Isocitrat-Dehydrogenase (IDH) in zerebralen Gliomen (513201378) (513201378)

Appears in the scientific report 2025
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 Record created 2025-01-22, last modified 2025-08-11


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